In our previous studies we have demonstrated the presence of calcitonin gene-related peptide (CGRP) immunoreactivity in nerve fibers in the rat pancreas innervating the acini, ducti, blood vessels and islets of Langerhans as well as in a cell population within the endocrine pancreas. CGRP is a biologically active peptide, being the most powerful vasoactive substance described to date and exerting potent effects on the digestive tract, influencing gastric and pancreatic secretions and food intake. The biological effects of CGRP and its dual localization to both neuronal pancreatic fibers and endocrine-like/paracrine-like cells within the endocrine pancreas strongly suggest that CGRP may play an important role in the pancreas, perhaps acting via both a neurocrine and endocrine or paracrine mechanism. The objective is to investigate CGRP expression and receptor (binding) sites distribution as well as its relationship with other peptides and peptide-hormones in the pancreas, to define CGRP role(s) and assess its site(s) and possible mechanism(s) of action in this viscerum. The specific aims are: 1) define the morphological organization of CGRP immunoreactivity within the pancreas in relation to other peptidergic systems and defined pancreatic structures; 2) analyze its receptor (binding) site distribution and density, 3) determine the identity and site of biosynthesis of this peptide; 4) examine the ontogeny of CGRP expression. The long term goal Is to define the interaction of this peptide with the endocrine and exocrine components of the pancreas in order to better understand the complex neural and hormonal regulation of pancreatic functions and to gain insight in the pathogenesis of pancreatic diseases.